Thiazolium-urea compound complexes

ABSTRACT

A UREA COMPOUND COMPLEX OF A COMPOUND WHICH IS A MEMBER SELECTED FROM THE GROUP CONSISTING OF   (2-(4-((R&#34;)2-N-),(R&#39;&#39;&#34;)2-PHENYL),3-R&#39;&#39;,4,5-DI(R-)-   THIAZOLIUM)M (X(-))M   WHEREIN X REPRESENTS A PHARMACEUTICALLY-ACCEPTABLE ANION; R, EACH BEING TAKEN SEPARATELY, REPRESENTS HYDROGEN OR LOWERALKYL, OR BOTH R MOIETIES, TAKEN TOGETHER, REPRESENT STRAIGHT-CHAIN ALKYLENE BEING OF FROM 3 TO 6, BOTH INCLUSIVE, CARBON ATOMS; R&#39;&#39; REPRESENTS PRIMARY LOWERALKYL; EACH R&#34; INDEPENDENTLY REPRESENTS HYDROGEN OR PRIMARY LOWERALKYL; EACH R&#39;&#39;&#34; INDEPENDENTLY REPRESENTS HYDROGEN BROMO, CHLORO, METHOXY, OR METHYL; AND M REPRESENTS AN INTEGER EQUAL TO THE VALENCE OF TEH ANION X. THE COMPLEXES ARE USEFUL AS AGENTS FOR REGULATING THE GROWTH OF PLANTS.

United States Patent 3,682,879 THIAZOLIUM-UREA COMPOUND COMPLEXES WalterReifschneider, Midland, Mich., assignor to The Dow Chemical Company,Midland, Mich. No Drawing. Original application Oct. 27, 1966, Ser. No.589,859, now Patent No. 3,511,850, dated May 12, 1970. Divided and thisapplication Aug. 29, 1969, Ser.

Int. Cl. C07c 127/00 U.S. Cl. 260-965 R 7 Claims ABSTRACT OF THEDISCLOSURE A urea compound complex of a compound which is a memberselected from the group consisting of R!!! R l l -QW This application isa division of parent application Ser. No. 589,859, filed Oct. 27, 1966-,now US. Pat. No. 3,51 1,850.

This invention is directed to a thiazolium compound which is a memberselected from the group consisting of a material of structural FormulaI:

Rig/0% iglljwh X H l R in its complex with a phenolic compound; itscomplex with a urea compound; and its complex with a metal saltcompound, The term thiazolium compound is employed herein to describe aproduct or products of this definition, only. In the above andsucceeding formulae, X represents a pharmaceutically acceptable anion;R, each being taken separately, represents a member selected from thegroup consisting of hydrogen and loweralkyl, or both R moieties, takentogether, represent straight-chain alkylene being of from 3 to 6, bothinclusive, carbon atoms; R represents primary loweralkyl; each R"independently represents a member selected from the group consisting ofhydrogen and primary loweralkyl; each R independently represents amember selected from the group consisting of hydrogen, bromo, chloro,methoxy and methyl; and m represents an integer equal to the valence ofthe anion X.

The term phenolic compound is employed in the present specification andclaims to designate a compound of the following formula only:

ice

wherein each Z independently represents, subject only to known factorsof steric hindrance, a member selected from the group consisting ofhalo, alkyl, and loweralkoxy; the symbol, 1 represents an integer offrom 1 to 6, both inclusive; the symbol g represents an integer of from0 to 5, both inclusive; and the symbol h represents an integer of from 0to 2, both inclusive, the sum of f, g and h being an integer of from 1to 6, both inclusive. The term alkyl is employed in the presentspecification and claims to designate an alkyl radical being of from 1to 6, both inclusive, carbon atoms.

Representative phenolic compounds include phenol, piodophenol,p-nitrophenol, pyrocatechol, resorcinol, hydroquinone, pyrogallol,1,2,4-benzenetriol, phloroglucinol, l,2,4,5-benzenetetrol, benzenehexol,o-methoxyphenol, 2, 4,5-trichlorophenol, 2,4-dinitrophenol, m-cresol,p-cresol, 4-n-hexylresorcinol, cre'sol, 4-bromo-m-cresol,4-ethylresorcinol, tetrachloropyrocatechol, 4-nitropyrocatechol, 2,S-dimethoxyhydroquinone, trichloropy-rogallol, anddimethylphloroglucinol.

In the present specification and claims, the term urea compound isemployed to designate only a member,

selected from the group consisting of urea, thiourea, guanidine,guanidine hydrochloride, and biuret; and the term metal salt compound isemployed only to designate a compound of the formula wherein Mrepresents a member selected from the group consisting of cooper copperiron iron antimony bismuth tin manganese zinc and cadmium Y represents apharmaceutically acceptable anion; and each of a and b represents aninteger such that (a times the valence of M) is equal to (1) times thevalence of Y).

In the present specification and claims, the unmodified term loweralkylis employed to designate alkyl radicals being of from 1 to 4, bothinclusive, carbon atoms. The term primary loweralkyl designates an alkylradical being of from 1 to 4, both inclusive, carbon atoms, and having aCH group at the point of attachment. Thus, the term primary loweralkyldesignates methyl, ethyl, npropyl, n-butyl, and isobutyl. As employed inthe present specification and claims, the term halide designatesappearances of chlorine, bromine, and iodine atoms, only.

In the instance of a complex with phenolic compound, urea compound, ormetal salt compound, such complex generally forms as a 1:1 complex, thatis, one molecule of material of Formula I and one molecule of complexingagent (phenolic compound, urea compound, or metal salt compound); as a2:1 complex, that is, two molecules of material of Formula I and onemolecule of complexing agent; or as a 1:2 complex, that is, twomolecules of complexing agent and one molecule of material of Formula I.Complexes having other ratios can be prepared and also are comprehendedwithin the definition of thiazolium compound of the present invention.It is noted that inasmuch as the material of Formula I has m units ofthe positive radical defined thereby the parentheses, a 1:1 complexcomprises more than one such positive radical whenever m represents aninteger in excess of 1.

Hence, the complex of the material of Formula I with the phenoliccompound, the urea compound, or the metal salt compound can bedescribed, in an alternate expression, as being most frequently of thefollowing formula:

wherein G, in each of its 11 occurrences, represents the same materialof Formula I; Z, in each of its e occurrences, represents the samemember selected from the group consisting of the phenolic compound, theurea compound, and the metal salt compound; and each of d and 2represents an integer being of from 1 to 2, both inclusive, the sum of dand e being an integer of from 2 to 3, both inclusive.

In the instance of a complex with a metal salt compound, each of theunits which constitute the complex, that is, (A) the material of FormulaI and (B) the metal salt compound, comprises an anion. These anions areinterchangeable. Therefore, in an alternate expression applicable to themetal salt complexes, these complexes can be described as being of thefollowing structural formula in which each of n, p, q, and z is aninteger and [n+(p times the valency of M)] is equal to the value of [(qtimes the valence of X)+(z times the valence of Y)]. In a preferredembodiment of such complexes, the anions X and Y are identical.

The primary attribute of the pharmaceutically-acceptable anion (X andalso, in the instance of the metal salt complexes, Y) is non-toxicity.The choice of the anion is not critical, although a given anion may insome instances exhibit special advantages, due to solubility, ease ofcrystallization, lack of objectionable taste and the like.Representative pharmaceutically acceptable anion moieties include thefollowing: chloride, bromide, iodide, sulfate, disulfate, acetate,salicylate, valerate, oleate, phenate, laurate, borate, benzoate,lactate, diglycollate, phos hate, phenylethylbarbiturate,o-acetoxybenzoate, citrate, dialkylbarbiturate, sulfathiazole,theophyllinate, urate, maleate, fumarate, succinate, tartrate,diethylbarbiturate, penicillinate, camphorate, carbonate, cacodylate,aconitate, sulfamate, gentisage, malate, cinnamate, stearate, and thelike.

Hence, representative metal salt complexes to be employed in accordancewith the present invention are those of a given product of Formula I andeach of the following metal salt compounds:

Antimony acetate, antimony trichloride, antimony tribromide, antimonytriiodide, antimony sulfate, antimony tartrate, bismuth acetate, bismuthbenzoate, bismuth tribromide, bismuth trichloride, bismuth citrate,bismuh triiodide, bismuth lactate, bismuth salicylate, bismuth sul-Complexes fate, bismuth tartrate, cupric acetate, cuprous acetate,cupric benzoate, cuprous bromide, cupric bromide, cupric butyrate,cuprous chloride, cupric chloride, cupric citrate, cupric formate,cupric glyceride, cupric lactate, cupric laurate, cupric oleate, cupricsalicylate, cupric stearate, cuprous sulfate, cupric sulfate, cuproussulfite, cupric tartrate, ferrous acetate, ferric acetate, ferricbenzoate, ferrous bromide, ferric bromide, ferrous carbonate, ferrouschloride, ferric chloride, ferric citrate, ferric formate, ferrousiodide, ferrous lactate, ferric lactate, ferric malate, ferric oleate,ferrous sulfate, ferric sulfate, ferrous tartrate, manganese acetate,manganese benzoate, manganese bromide, manganese chloride, manganesecitrate, manganese formate, manganese iodide, manganese lactate,manganese orthophosphate, manganese metasilicate, manganese sulfate,manganese tartrate, manganese valerate, stannous acetate, stannousbromide, stannous chloride, stannous chromate, stannous iodide, stannousorthophosphate, stannous sulfate, stannnous tartrate, zinc acetate, zincaluminate, zinc benzoate, zinc borate, zinc bromide, zinc butyrate, zinecaproate, zinc carbonate, zinc chloride, zinc chromate, zinc citrate,zinc formate, zinc iodide, zinc lactate, zinc laurate, zinc oleate, zincsalicylate, zinc stearate, zinc sulfate, zinc sulfite, and zinctartrate.

The thiazolium compound of the present invention can exist as a hydrate,ordinarily as a hemihydrate, monohydrate, or dihydrate, and it isfrequently convenient to prepare and separate a given product as ahydrate. Sometimes the hydrate contains a higher proportion of water permolecule of complex, such as 2 to 10 moles of water per mole of complex.Also, the products, particularly those in which X, or one or both of Xand Y in the instance of the metal salt complexes, represent(s) ahalogen atom, sometimes exist at least initially as a hydrohalideaddition salt at the site of the para amino nitrogen. However, thesehydrohalide salts readily dehydrohalogenate upon recrystallization oreven merly upon standing. Because of this instability, their use is notgenerally preferred. However, regardless of the existence of a givenmaterial as a hydrate or hydrohalide addition salt, or of the ratio ofcomplexing in the instance of a complex, all of such materials arecomprehended within the definition hereinabove of thiazolium compoundand can be employed for the useful purposes of the present invention.

The products of the present invention are typically crystalline solidmaterials at room temperature. They are prepared in accordance with thereaction sequence illustrated by the following equation:

thiazole starting compound Hence, the products of Formula I wherein Xrepresents p-toluenesulfonate are prepared first, and from them, theremaining products of Formula I are synthesized. The complexes areprepared by reacting the corresponding products of Formula I with theappropriate complexing agent.

The first step of the reaction sequence, the reaction of the thiazolecompound and the primary loweralkyl ptoluenesulfonate, is carried out inconventional procedures for quaternization. The reaction can be carriedout in the presence of a suitable organic liquid as a reaction medium;the identity of such medium, if employed, is not critical, although apolar substance is generally preferred, most typically, nitrobenzene oran excess amount of the primary loweralkyl p-toluenesulfonate reactantis employed. 'Equimolecular proportions of the reactants are consumed inthe reaction; however, complete quaternization of the thiazole compoundis more readily assured by the use of a slight excess of the primaryloweralkyl ptoluenesulfonate. Therefore, it is preferred to employ onemolecular proportion of thiazole and from 1.2 to 1.5 molecularproportions of the primary loweralkyl p-toluenesulfonate. The reactiongoes forward at temperatures of from 100 to about 160 C. The resultingp-toluenesulfonate product, a material of Formula I wherein X representsptoluenesulfonate, is separated from the reaction mixture inconventional procedures. Most typically, the reaction medium is removedby evaporation under subatmospheric pressure to obtain the product as aresidue. This product residue can be purified by conventional proceduressuch as recrystallization. Alternately, the product of thequaternization is not separated from the reaction mixture but is reactedin situ with the MX compound to prepare the other products of Formula I.

The reaction with the MX compound and the p-toluenesulfonate productinitially prepared represents the second step of the reaction sequence.This step, in which all remaining products of Formula I are prepared, isconducted in accordance with standard procedures for the exchange ofanions. In this step, the MX reactant is a metal (M) salt having thedesired X anion. The identity of the metal is not critical, but sodiumand potassium salts are most conveniently employed. The reaction goesforward readily at temperatures of a wide range, limited only by suchreadily apparent factors as, at lower limits, freezing of the reactionmixtures, and, at upper limits, decomposition of one of the reactants orthe resulting product. Generally, though, it is preferred to conduct thereaction at temperatures of from 90 to 100 C. A reaction medium ispreferably employed. It is desirable that both reactants be soluble inthe medium; therefore, water or a loweralkanol is typically employed.The reaction consumes the reactants in amounts representingstoichiometric proportions, and, in the instance wherein the desiredproduct is essentially insoluble in the reaction medium employed, theemployment of the reactants in amounts representing such proportions isadequate and gives good results. However, in the instance wherein thedesired product is soluble to a greater or lesser extent in the reactionmedium it is preferred to use an excess of the metal salt reactant, suchas, for example, a ten-fold excess, in order that the product is forced,by the presence of the excess metal salt anion, to precipitate in thereaction mixture. The precipitated product is then readily separated byfiltration. A by-product metal p-toluenesulfonate salt is produced inthe course of the reaction. This by-product typically remains dispersedin the reaction medium and is separated on the filtration step. Theseparated product is purified, when desired, by conventional procedures,typically recrystallization.

In the third step of the reaction sequence, those products of thepresent invention which are complexes are prepared by reacting thecorresponding product of Formula I with the desired complexing agent,that is, phenolic compound, urea compound, or metal salt compound. The

reaction is conveniently carried out by contacting the reactants in aninert liquid reaction medium. Suitable reaction media include water; theloweralkanols such as methanol, ethanol, and isopropanol; and theloweralkyl ketones, such as acetone and methyl ethyl ketone. Thereaction goes forward under temperatures of a wide range, but ispreferably carried out at temperatures of from about 20 C. to theboiling temperature of the reaction medium employed.

The reaction proceeds with the production of some of the desired productwhen the reactants are employed in any amounts. When it is desired toprepare a product in which the complex is of a given ratio, it ispreferred to employ the reactants in approximately those amounts whichare consumed in the preparation of the given ratio of complex, or inamounts which represent a slight excess of complexing agent. In theinstance of a 1:1 complex, equimolecular proportions of the reactantsare consumed. In the instance of a 1:2 complex, one molecular proportionof product of Formula I and two molecular proportions of complexingagent are consumed; and in the instance of a 2:1 complex, one molecularproportion of complexing agent and two molecular proportions of prod notof Formula I are consumed.

In carrying out the reaction, the reactants are mixed and contactedtogether in any manner, conveniently by adding one reactant to the otherreactant in the presence of the reaction medium. Thereafter, theresulting reaction mixture can be maintained for a period of time in thereaction temperature range to complete the reaction, although thereaction ordinarily goes to completion with the completion of thecontacting together of the' reactants. The product typically appears asa precipitate in the reaction mixture. This product can be separated byfiltration or decantation. If desired, the separated product can bepurified by washing with inert liquid reaction medium or byrecrystallization.

The following examples illustrate the present invention and will enablethose skilled in the art to practice the same.

EXAMPLE 1 2- (p-dimethylaminophenyl)-3,4,5-trimethylthiazoliump-toluenesulfonate A first solution was prepared by dispersing 40 gramsof methyl p-toluenesulfonate (0.215 mole) in 50 milliliters ofnitrobenzene. A second solution was similarly prepared by dispersing37.5 grams of Z-(p-dimethylaminophenyl)- 4,5-dirnethylthiazole (0.16mole) in milliliters of nitrobenzene and thereafter heating the solutionto a temperature of C. Subsequently, the first solution was added to thesecond solution; the addition was carried out portionwise, so that thetemperature of the resulting reaction mixture remained at about 160 C.After the completion of the addition, the reaction mixture was held for4 hours at a temperature of about 160 C. and the nitrobenzene thenremoved by steam distillation to obtain the desired2-(p-dimethylaminophenyl) 3,4,5 trimethylthiazolium p-toluenesulfonateproduct. The product has a molecular weight of 418.6.

EXAMPLE 2 2- (p-dimethylaminophenyl) -3,4,5-trimethylthiazolium iodideThe product obtained as reported in Example 1 was dissolved in hot waterand the resulting solution filtered. Potassium iodide (60 grams; 0.36mole) was added to the filtrate. The addition resulted in theprecipitation in the reaction mixture of the desiredZ-(p-dimethylaminophenyl) 3,4,5 tn'methylthiazolium iodide product. Theproduct was separated by filtration and the separated productrecrystallized from methanol. The recrystallized material was found tomelt at 225-226 C.

Elemental analysis of the product was made. The results were as follows:

7 Calculated (percent): C, 44.92; H, 5.12; I, 33.91. Found (percent): C,44.9; H, 5.32; I, 33.42.

EXAMPLE 3 2- (p-dimethylaminophenyl)-3,4,5-trirnethy1- thiazoliumchloride 2 (p dimethylaminophenyl) 3,4,5 trirnethylthiazoliurnp-toluenesulfonate and sodium chloride were re- 2-(p-dimethylaminophenyl)-3,4,5-trimethylthiazolium chloride 1:1 complexwith zinc chloride A first solution of zinc chloride (14 grams; 0.105mole) and 50 milliliters of methanol was added portionwise at roomtemperature to a second solution of 2-(p-dimethylaminophenyl) 3,4,5trimethylthiazolium chloride (20 grams; 0.07 mole) and 100 millilitersof methanol. The addition resulted in the precipitation in the reactionmixture of the desired2-(p-dimethylaminophenyl)-3,4,5-trimethylthiazolium chloride 1:1 complexwith zinc chloride. The product was separated by filtration and theseparated product purified by recrystatllization from methanol. Thepurified product was found to melt at 177- 179 C.

In view of the foregoing teachings and examples, those skilled in theart will be enabled to prepare all of the products of the presentinvention. Other representative products include those set forth in thefollowing table.

Identifying characteristic Name of product: of product 2 (pdimethylaminophenyl) 3,4,5 tri- 2 (p dimethylaminophenyl) 3,4dimethylthiazolium iodide, M.P. At 208210 C. 2 (p dimethylaminophenyl)3,4 dimethyl thiazolium sulfate, M.W. 562.8 2 (p dimethylaminophenyl) 3methyl- 4,5,6,7 tetrahydrobenzothiazolium iodide, M.P. 2182l9 C. 2 (2,5dichloro 4 isobutylaminophenyl)- 5 methyl 3 ethylthiazolium valerate 1:1complex with manganese valerate, M.W. 674.6 2 (3 methyl 4dipropylaminophenyl)- 3,4,5-trimethylthiazolium iodide, M.W. 2 (2 bromo5 methoxy 4 dimethylaminophenyl) 3,4,5 trimethylthiazolium oleate 1:1complex with ferric oleate, M.W. 2 (3,5 dimethyl-4-dimethylaminophenyl)-3,4-dimethylthiazolium bromide 2:1 commethylthiazoliump-toluenesulfonate 1:1 c o m p l e x with urea, hemihydrate,

M.P. 167l68.5 C.

2 (p dimethylaminophenyl) 4,5,6,7- tetrahydro 3 methylbenzothiazoliumptoluenesulfonate, M.W.

2 (p dimethylaminophenyl) 4,5,6,7-

tetrahydro 3 methylbenzothiazolium iodide 1:1 complex with bismuthiodide, M.W.

2 (p dimethylaminophenyl) 4,5 diethyl- 3 n propylthiazolium salicylate,M.W.

2 (p dimethylaminophenyl) 4,5 diethyl- 3 n propylthiazolium salicylate1:1 complex with bismuth salicylate, M.W

2 (p diethylaminophenyl) 4,5 dimethyl- 3 n butylthiazolium chloride,M.W.

2 (p dimethylaminophenyl) 5 n butyl- 3,4 dimethylthiazolium formate 1:1complex with guanidine hydrochloride, M.W.

2 (p dimethylaminophenyl) 3 methylthiazolium carbonate 1:1 complex withferric carbonate, M.W.

2 (p diethylaminophenyl) 3,4,5 trimethylthiazolium butyrate 1:1 complexwith m-cresol, M.W.

2 (3 methyl 4 dimethylaminophenyl)- 3 methylcycloheptathiazoliumdihydrogen phosphate 1:1 complex with stannous phosphate, M.W

2 (p dimethylaminophenyl) 3 methylthiazolium acetate 1:1 complex withomethoxyphenol, M.W.

2 (p dimethylaminophenyl) 3 methylthiazolium iodide 1:1 complex withp-iodophenol, M.W.

2 (p diethylaminophenyl) 3,4 dimethylthiazolium bromide 2:1 complex withthiourea, M.W.

2 (p dimethylaminophenyl) 3,4,5 trimethylthiazolium chloride 1:1 complexwith biuret, M.W.

2 (p dimethylaminophenyl) 3 methylthiazolium iodide 1:1 complex withresorcinol, M.W.

2 (p dimethylaminophenyl) 4,5,6,7- tetrahydro 3 ethylbenzothiazoliumhydrogen sulfate 1:1 complex with phenol, M.W.

2 (2,5 dichloro-4-dimethylaminophenyl)- 3-methylthiazo1ium benzoate 1:1complex with guanidine, M.W

2-(p-dimethylaminophenyl) 4 n propyl- 3 methylthiazolium lactate 1:1complex with manganese lactate, M.W

2 (2 methoxy 4 dimethylaminophenyl)- 3,4 dimethylthiazolium bromide 1:1complex with pyrocatechol, M.W.

2 (p dimethylaminophenyl) 3,4,5 trimethylthiazolium hydrogen sulfate 1:1complex with pyrogallol, M.W

2 (p dimethylaminophenyl) 3 methylthiazolium p-toluenesulfonate 1:1complex with hydroquinone, M.W.

The products of the present invention are useful as agents to regulatethe growth of plants. Accordingly, they can be employed as herbicides,as fungicides, and as bactericides. In such application, the unmodifiedproducts can be employed. Generally, though, it is preferred to employthe products in the form of a composition comprising the product orproducts and one or more adjuvants, such as water, organic solvents,surface active agents, and the like. As herbicides, they are effectivefor the control of such plants as crabgrass and barnyard grass. Inrepresentative operations, 2-(pdimethylaminophenyl)-3,4-dimethylthiazolium iodide was dispersed inwater to obtain an aqueous treating composition containing 4000 partsthereof per million parts by weight of ultimate composition. Plots ofyoung crabgrass were sprayed to the point of runoff with thiscomposition, and the sprayed plants held for a period of about two weeksunder good agricultural conditions. Other plots of young crabgrassplants were left untreated to serve as a control and held for the sameperiod under the same conditions. At the end of this period, observationof the treated plots showed substantially complete kill and control ofthe growth of crabgrass, whereas in the control plots, the plants werethriving and in good health.

The products of the present invention are also useful as agents toimprove the health of warm-blooded animals. In one embodiment, theproducts are incorporated in animal feeds or drinking water; such usage,the products improve the growth characteristics of the animals,especially by controlling the organisms which are internal parasitesupon the animals. In another embodiment, the control of these parasitescan also be achieved by contacting the parasites in their infectivephase outside of the host animal body.

The thiazole compounds which are employed as starting materials toprepare the products of the present invention are themselves prepared inknown procedures. In these procedures, an alpha-haloketone of thefollowing formula:

l R R-(iJ-halo is condensed with a para-aminothiobenzamide compound ofthe formula:

S R! NHr-ii-@-NR" The condensation is carried out by reacting thealphahaloketone with the para-aminothiobenzamide in the presence of analkali metal acetate. The reaction is conveniently carried out in thepresence of an organic liquid as a reaction medium; suitable such mediainclude the alkanols, glycols, and glycol ethers. The reaction consumesthe reactants and alkali metal acetate in amounts representingequimolecular proportions of each of the alpha-haloketone,para-aminothiobenzamide, and alkali metal acetate. The reaction goesforward readily at temperatures of from about room temperature to theboiling temperature of the reaction medium employed. The resultingthiazole starting material is separated from the reaction mixture inconventional procedures. Typically, solvent is removed from the reactionmixture by evaporation under subatmos- 10 pheric pressure and theresulting residue, comprising the desired product and alkali metalby-product salt, washed with water separate the desired product as aresidue. This product residue can be purified in conventionalprocedures, typically by recrystallization from a suitable solvent, suchas a loweralkanol.

'I claim:

1. The complex of (1) a urea compound of the group consisting of urea,thiourea, guanidine, guanidine hydrochloride and biuret with (2) acompound corresponding to the formula:

wherein X represents a pharmaceutically-acceptable anion; each Rindependently represents hydrogen or loweralkyl, or both R moieties,taken together, represent straightchain alkylene of from 3 to 6 carbonatoms; R represents primary loweralkyl; each R" independently representshydrogen or primary loweralkyl; each R independently representshydrogen, bromo, chloro, methoxy, or methyl; and m represents an integerequal to the valence of the anion X.

2. The composition of matter claimed in claim 1 which is 2(p-dimethylaminophenyl) 4,5 dimethyl 3- isobutylthiazolium iodide 1:2complex with urea.

3. The composition of matter claimed in claim 1 which is 2(p-dimethylaminophenyl) 3,4,5-trimethylthiazolium p-toluenesulfonate 1:1complex with urea.

4. The composition of matter claimed in claim 1 which is 2(p-dimethylaminophenyl) 5 nabutyl 3,4-dimethylthiazolium formate 1:1complex with guanidine hydrochloride.

5. The composition of matter claimed in claim 1 which is 2(p-diethylaminophenyl) 3,4 dimethylthiazolium bromide 2:1 complex withthiourea.

6. The composition of matter claimed in claim 1 which is 2(p-dimethylaminophenyl) 3,4,5-trimethylthiazolium chloride 1:1 complexwith biuret.

7. The composition of matter claimed in claim 1 which is 2 (2,5 dichloro4 dimethylaminophenyl) 3- methylthiazolium benzoate 1:1 complex withguanidine.

References Cited UNITED STATES PATENTS 8/1967 Reifschneider 260-965 R 5/197-0 Reifschneider 260-965 R Parent No.

Inventofls) Wej "her Reifschneiier 5 August 1.9?2

in the above-identified patent corrected as shown below:

r Column 3, line 33, delete "disulfete" and insert --bisulf ate-.

Column 7, line 40, delete "eubrie *end insert cupric -e Col 9. line 55"plants-- were 0 should be inserted before line 18 "an" sheuld beinserted before such.

Sighed and sealed this 29th day of May 1973.

(SEAL) Arrest:

EDWARD M.FLETCHER,JR. Arresting Officer ROBERT GOTTSCHALK Commissionerof Patents

